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Neuropathology of nondemented aging: Presumptive evidence for preclinical Alzheimer disease
Open accessAbstract
Objective To determine the frequency and possible cognitive effect of histological Alzheimer’s disease (AD) in autopsied older nondemented individuals. Design Senile plaques (SPs) and neurofibrillary tangles (NFTs) were assessed quantitatively in 97 cases from 7 Alzheimer’s Disease Centers (ADCs). Neuropathological diagnoses of AD (npAD) were also made with four sets of criteria. Adjusted linear mixed models tested differences between participants with and without npAD on the quantitative neuropathology measures and psychometric test scores prior to death. Spearman rank-order correlations between AD lesions and psychometric scores at last assessment were calculated for cases with pathology in particular regions. Setting Washington University Alzheimer’s Disease Research Center. Participants Ninety-seven nondemented participants who were age 60 years or older at death (mean = 84 years). Results About 40% of nondemented individuals met at least some level of criteria for npAD; when strict criteria were used, about 20% of cases had npAD. Substantial overlap of Braak neurofibrillary stages occurred between npAD and no-npAD cases. Although there was no measurable cognitive impairment prior to death for either the no-npAD or npAD groups, cognitive function in nondemented aging appears to be degraded by the presence of NFTs and SPs. Conclusions Neuropathological processes related to AD in persons without dementia appear to be associated with subtle cognitive dysfunction and may represent a preclinical stage of the illness. By age 80–85 years, many nondemented older adults have substantial AD pathology.
Overview
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TL;DR
In 97 nondemented older adults autopsied across seven Alzheimer’s Disease Centers, a substantial minority had Alzheimer-type neuropathology, and higher plaque or tangle burden was linked to slightly poorer cognitive scores despite no clinical dementia. The results support the possibility of a presymptomatic Alzheimer stage, though the study cannot prove that these cases would have progressed.
Key findings
- Depending on the criteria used, 39–47% of cases met some neuropathological AD threshold; stricter thresholds identified about 19–21%. Khachaturian criteria classified 47%, Washington University criteria 39%, CERAD any level 39% (19% possible, 19% probable, 2% definite), and NIA-Reagan any level 39% (20% low, 16% intermediate, 3% high).
- Cases with and without neuropathological AD did not differ in age at death, interval from last assessment to death, education, or last psychometric performance.
- Among cases with lesions in the relevant regions, greater AD pathology correlated with worse performance on episodic memory, category fluency, Trailmaking A and B, and the MMSE; neocortical diffuse senile plaque density best discriminated neuropathological AD from no neuropathological AD.
- Braak stages ranged from 0 to V with a median of II. Older age correlated with higher Braak stage (r = .372, p < .001), limbic NFT density increased with age (r = .437, p < .001), plaque burden did not correlate with age (r = .089, p = .40), and neocortical plaque burden was weakly related to limbic NFT density (r = .196, p = .07).
Methods
- The sample included 97 autopsied nondemented participants aged 60 or older at death (mean 84.3 ± 8.6 years; 55 women; mean education 15.4 ± 2.9 years; mean last MMSE 28.1 ± 2.1) from 7 Alzheimer’s Disease Centers, all with CDR 0 within 2 years of death; 11 CDR > 0 cases were assessed but not reported.
- A central laboratory processed five brain regions uniformly, used silver and immunohistochemical stains, made consensus diagnoses with four criteria sets (Khachaturian, Washington University, CERAD, NIA-Reagan), assigned Braak stages, and quantified plaques and tangles using computerized stereology.
- Analyses used linear mixed models adjusted for center and covariates, ROC/sensitivity analyses for diffuse plaques, and Spearman correlations between lesion densities and last psychometric scores.
Limitations
- The authors state that the study used a convenience sample, could not assess genotype effects, had small samples for some cognitive associations, and faced variability in initial fixation and tissue processing across centers. They also note that plaques and tangles may be downstream of the pathogenic processes causing synaptic and neuronal degeneration, and that the study did not address early protein changes, later neuronal or synaptic loss, vascular lesions, or synucleinopathy.
- The authors caution that findings from nondemented individuals may not extend to cases with manifest dementia, and that missing psychometric data and small numbers with both lesions and test results require interpretive caution.
- Evident from the text: the cross-sectional autopsy design cannot establish whether pathology precedes or predicts dementia, and correlations weakened when all cases were included or when adjusting for age or education.
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41 Own result · 32 Not checked yet · 16 Own method · 12 Own interpretation · 1 No basis given
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In the paper
“Likewise, results were similar for the correlation of NFTs with the psychometric test scores after adjustment for plaque burden within the same region.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Results > Quantitative Neuropathological Assessment
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In the paper
“In contrast, plaque burden was not significantly correlated with age (Figure 4B; Spearman correlation=0.089, p=0.40).”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Results > Quantitative Neuropathological Assessment
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In the paper
“there was substantial overlap of the Braak stages between the npAD and no-npAD cases (Figure 3).”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Results > Neuropathological Assessment
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In the paper
“Spearman correlations between the quantitative neuropathological measures and all outcomes of CERAD criteria (no AD or Possible, Probable, or Definite) and all outcomes of NIA-Reagan criteria (no AD or Low, Intermediate, or High) yielded almost the identical rank order for association with diagnostic level (Table 2).”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Results > Quantitative Neuropathological Assessment
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In the paper
“when strict criteria were used, about 20% of cases had npAD.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Abstract > Results
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In the paper
“Neocortical plaque burden and limbic NFT density in nondemented cases were weakly correlated (Spearman correlation=0.196, p=.07, Figure 5).”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Results > Quantitative Neuropathological Assessment
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In the paper
“The least strict of the 4 sets of criteria, those proposed by Khachaturian, resulted in a neuropathological diagnosis of AD in 46 of the 97 cases (47%).”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Results > Neuropathological Assessment
plainn = 97- Asserted: passes — The authors put it forward as true.
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In the paper
“and 19% by the NIA-Reagan Intermediate/High criteria.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Results > Neuropathological Assessment
plainn = 97- Asserted: passes — The authors put it forward as true.
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In the paper
“The density of NFTs in limbic areas was the least discriminative (Table 2).”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Results > Quantitative Neuropathological Assessment
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In the paper
“No cases met criteria for stage VI (very pronounced neurofibrillary changes throughout all parts of cortex and in many subcortical structures).”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Results > Neuropathological Assessment
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In the paper
“using these definitions, 21% were diagnosed with npAD by the CERAD Probable/Definite criteria, and 19% by the NIA-Reagan Intermediate/High criteria.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Results > Neuropathological Assessment
plainn = 97- Asserted: passes — The authors put it forward as true.
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In the paper
“About 40% of nondemented individuals met at least some level of criteria for npAD; when strict criteria were used, about 20% of cases had npAD.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Abstract > Results
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In the paper
“There was virtually no difference between the Braak stages of cases at comparable levels of the CERAD and NIA-Reagan criteria (Figure 3B,C).”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Results > Neuropathological Assessment
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In the paper
“In all cases, greater pathology was associated with poorer cognitive performance at last assessment on measures of episodic memory (Logical Memory Delayed), semantic knowledge (Category Fluency), visuospatial ability (Trailmaking A), and executive function (Trailmaking B) as well as on a general measure, the MMSE.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Results > Quantitative Neuropathological Assessment
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In the paper
“The correlations between the psychometric test scores and plaque burden, and between the test scores and diffuse SPs, were similar after adjustment for NFTs in the same brain region using partial correlation coefficients.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Results > Quantitative Neuropathological Assessment
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In the paper
“Older age was significantly correlated with higher Braak stages (Spearman r=.372, p<.001), consistent with observations that NFTs increase with age, even in the absence of SPs.(Arriagada et al., 1992; Price & Morris, 1999)”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Results > Neuropathological Assessment
What the sources say
- Not checked yetcites Arriagada et al., 1992 source
- Not checked yetcites Price & Morris, 1999
plaincorrelationaln = 97- Asserted: passes — The authors put it forward as true.
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In the paper
“NFT density increased with age in limbic areas (entorhinal and perirhinal cortex, amygdala, and hippocampus field CA1) (Figure 4A; Spearman correlation=0.437, p<.001).”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Results > Quantitative Neuropathological Assessment
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In the paper
“Although none of the participants in this study had clinically detectable dementia or cognitive impairment that was measurable on an individual basis, a significant correlation of some psychometric test scores was found with the density of AD lesions across the group, indicating that cognitive function in nondemented aging may decline with increasing numbers of NFTs or SPs, including diffuse SPs (”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Results > Quantitative Neuropathological Assessment
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In the paper
“Although a greater likelihood of npAD was associated with higher Braak stage scores for all 4 criteria (chi-square, p<0.003), there was substantial overlap of the Braak stages between the npAD and no-npAD cases (Figure 3).”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Results > Neuropathological Assessment
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In the paper
“The Washington University criteria yielded a neuropathological diagnosis of AD in 38 cases (39%), identical to the number of cases meeting any of the 3 levels of npAD using CERAD criteria (19% Possible, 19% Probable, and 2% Definite AD; 39% with all levels combined,) and any of the 3 levels of the NIA-Reagan criteria (20% Low, 16% Intermediate, and 3% High; 39% combined).”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Results > Neuropathological Assessment
plainn = 38- Asserted: passes — The authors put it forward as true.
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In the paper
“ROC analyses indicated that the density of neocortical diffuse SPs best discriminated between npAD and no-npAD (defined by combination of all three diagnostic levels of either criteria), followed by the density of diffuse SPs in limbic areas.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Results > Quantitative Neuropathological Assessment
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In the paper
“Third, AD lesions (including diffuse SPs) in nondemented aging are associated with a deleterious effect on cognitive performance when examined across the group and hence are unlikely to be benign.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
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- Rests on an assumption: The cognitive deficits associated with AD lesions in nondemented individuals are attributable to those lesions rather than to other pathologies or measurement error.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Second, diffuse SPs are a prominent feature of npAD in nondemented cases and discriminate cases with and without npAD.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
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In the paper
“Second, diffuse SPs are a prominent feature of npAD in nondemented cases and discriminate cases with and without npAD.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Although there was no measurable cognitive impairment prior to death for either the no-npAD or npAD groups, cognitive function in nondemented aging appears to be degraded by the presence of NFTs and SPs.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Abstract > Results
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In the paper
“Nondemented older adults have a wide range of Braak stages, even in individuals with high SP densities.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“many of the nondemented older adults in this sample, including the eldest at age 106 years, had few if any SPs (Figure 4,B).”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
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In the paper
“The individuals with npAD in this study did not differ in age from those without npAD, suggesting that age alone cannot account for the frequency of npAD.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
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In the paper
“Although the small sample sizes impose interpretative caution, we found preliminary evidence for subtle cognitive impairment during the preclinical stage of npAD that correlates with NFT densities, plaque burden, and SP densities among individuals with those lesions.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The cognitive deficits associated with AD lesions in nondemented individuals are attributable to those lesions rather than to other pathologies or measurement error.
None of the sources cited for this claim have been checked yet.
In the paper
“Senile plaques (SPs) and neurofibrillary tangles (NFTs), the neuropathological hallmarks of Alzheimer’s disease (AD),(Khachaturian, 1985) are not limited to individuals with dementia of the Alzheimer type (DAT) but also may be present in the brains of cognitively normal older adults.(Tomlinson et al., 1968; Crystal et al., 1988; Katzman et al., 1988; Price et al., 1991; Dickson et al., 1992; Tronc”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Introduction
What the sources say
hedged- Asserted: passes — The authors put it forward as true.
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In the paper
“the mechanisms responsible for SPs and NFTs in nondemented older adults appear identical to those found in AD(Haroutunian et al., 1998; Haroutunian et al., 1999)”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Introduction
What the sources say
hedged- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Plaque burden and NFT density were least dependent on fixation differences between different cases.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Material and Methods > Quantitative Assessment
plain- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“the distribution of SPs and NFTs in nondemented older adults corresponds with the hierarchical topographical progression associated with symptomatic AD.(Arriagada et al., 1992; Price & Morris, 1999; Price et al., 1991)”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Introduction
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Such methodological differences, combined with relatively small sample sizes in all but one study,(Bennett et al., 2006) may contribute to conflicting results on the relationships between SPs or NFTs and cognition in nondemented aging.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Introduction
What the sources say
- Not checked yetcites Bennett et al., 2006 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“By age 80–85 years, many nondemented older adults have substantial AD pathology.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Abstract > Conclusions
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- Rests on an assumption: The autopsied sample from seven Alzheimer Disease Centers is representative of nondemented older adults in the general population.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although there was no measurable cognitive impairment prior to death for either the no-npAD or npAD groups, cognitive function in nondemented aging appears to be degraded by the presence of NFTs and SPs.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Abstract > Results
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The observed associations between Alzheimer disease lesions and cognitive test scores are not due to other brain pathologies or unmeasured confounders.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Third, AD lesions (including diffuse SPs) in nondemented aging are associated with a deleterious effect on cognitive performance when examined across the group and hence are unlikely to be benign.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The cognitive deficits associated with AD lesions in nondemented individuals are attributable to those lesions rather than to other pathologies or measurement error.
None of the sources cited for this claim have been checked yet.
In the paper
“However, SPs and NFTs characterize the neuropathological substrate of AD and synaptic and neuronal loss developing from these or other lesions appear to be critical for the expression of cognitive symptoms.(Masliah et al., 2001; Price et al., 2001)”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
What the sources say
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The finding that up to 40% of nondemented individuals with a mean age of death of 84 years have npAD corresponds with some estimates of the prevalence of clinically apparent DAT in this age group.(Hebert et al., 2003)”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
What the sources say
- Not checked yetcites Hebert et al., 2003 source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Senile plaques may not be ubiquitous with age;(Braak & Braak, 1997; den Dunnen et al., 2008)”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
What the sources say
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“In contrast, NFTs initially develop in limbic areas, and later extend into neocortical areas; they increase as a function of age even in the absence of SPs.(Price & Morris, 1999; Bennett et al., 2004)”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
What the sources say
- Not checked yetcites Price & Morris, 1999
- Not checked yetcites Bennett et al., 2004 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“In contrast, NFTs initially develop in limbic areas, and later extend into neocortical areas; they increase as a function of age even in the absence of SPs.(Price & Morris, 1999; Bennett et al., 2004)”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
What the sources say
- Not checked yetcites Price & Morris, 1999
- Not checked yetcites Bennett et al., 2004 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Exclusion of diffuse SPs from CERAD and NIA-Reagan criteria may omit an important indicator of npAD.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Presumably the absence of dementia in preclinical npAD reflects a delay between the appearance of Aβ and neurofibrillary lesions and the subsequent neuronal or synaptic degeneration that results in clinical symptoms of dementia.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The individuals with npAD in this study did not differ in age from those without npAD, suggesting that age alone cannot account for the frequency of npAD.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Second, all participants had been carefully studied longitudinally with clinical and neuropsychological instruments to exclude contamination of the sample by individuals with unrecognized very mild dementia or mild cognitive impairment.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
plainn = 97- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“An important caveat for the observations reported here is that they are from nondemented individuals and thus may not extrapolate to cases in which dementia already is manifest.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that any set of neuropathological criteria using quantitative levels of SPs and NFTs likely establishes an artificial diagnostic boundary.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Because there appears to be little neuronal degeneration in preclinical AD,(Gomez-Isla et al., 1996; Price et al., 2001; West et al., 2004) this stage of the illness could be an attractive target for treatment with agents developed to modify or arrest the AD process.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
What the sources say
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It may not be possible to recognize preclinical AD with standard clinical and cognitive measures, even in expert settings (e.g., ADCs).”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Probably not a substantial claim. 31
- It may state two separate claims as one. 26
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The mean interval from last ADC assessment to death in the 97 cases was 0.7 +/− 0.5 years.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Material and Methods > Participants
plainn = 97- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Ninety-seven nondemented participants who were age 60 years or older at death (mean = 84 years).”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Abstract > Participants
plainn = 97- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There were no differences in mean age at death, interval between last clinical assessment and death, education, or psychometric performance at last assessment before death between cases with npAD versus those without npAD using any of the 4 criteria (even when restricted to Probable and Definite CERAD and Intermediate and High NIA-Reagan criteria) (Table 1).”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Results > Neuropathological Assessment
plainn = 97- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The 4 stage 0 cases were relatively young, aged 66, 69, 72, and 72 years at death.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Results > Neuropathological Assessment
plainn = 4- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and any of the 3 levels of the NIA-Reagan criteria (20% Low, 16% Intermediate, and 3% High; 39% combined).”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Results > Neuropathological Assessment
plainn = 97- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Adjusting for age at death, all correlations reported in Table 3 remain significant except for that between limbic diffuse SPs and Trailmaking B (Spearman correlation=0.29, p=.16); conversely, the correlation become significant between limbic NFTs for Trailmaking A (Spearman correlation=−0.39, p=.003) and Digit Symbol (Spearman correlation=0.39, p=.04).”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Results > Quantitative Neuropathological Assessment
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Inclusion of all cases in the analyses, regardless of whether they demonstrated AD lesions, attenuated the correlations, as expected. Nonetheless, neocortical plaque burden remained significantly correlated with Logical Memory-Delayed (Spearman correlation=−0.42, p=0.03). Limbic NFTs also remained significantly correlated with MMSE (Spearman correlation=−0.38, p<.001), and neocortical NFTs were”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Results > Quantitative Neuropathological Assessment
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Adjusting for education, all correlations reported in Table 3 still remain significant except for these between limbic diffuse SPs and Trailmaking B (Spearman correlation=0.36, p=.08) and between neocortical diffuse SPs and Logical Memory Delayed (Spearman correlation=−0.46, p=.06).”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Results > Quantitative Neuropathological Assessment
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Braak neurofibrillary stages in the 97 cases ranged from 0 (no NFTs observed) to V (widespread neocortical tangles), with a median value of Stage II (Stage 0, n=4; Stage I, n=31; Stage II, n=36; Stage III, n=15; Stage IV, n=8; Stage V, n=3).”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Results > Neuropathological Assessment
plainn = 97- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“identical to the number of cases meeting any of the 3 levels of npAD using CERAD criteria (19% Possible, 19% Probable, and 2% Definite AD; 39% with all levels combined,)”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Results > Neuropathological Assessment
plainn = 38- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“First, consistent with previous reports, a substantial proportion of nondemented older adults were found to have npAD, with the frequency ranging from about 20% (when criteria are restricted to Probable/Definite CERAD and Intermediate/High NIA-Reagan) to about 40% (all levels of criteria).”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The autopsy sample of nondemented older adults is representative enough that the estimated frequency of npAD applies to nondemented older adults generally.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Diffuse SPs and consequently plaque burden appear initially in the neocortex and best discriminate npAD and no-npAD in nondemented aging.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“NFTs were present in almost all of the cases in this series, although 4 of the youngest cases had few if any (Braak Stage 0).”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
plaincorrelationaln = 4- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Once present in the brain, both SPs and NFTs occur in a continuous manner, without a clear boundary between “npAD” and “no-npAD” (Figure 5).”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Neuropathological criteria for AD rely on densities of SPs and NFTs to discriminate AD from aging, as the distinction between the two conditions has been thought to be quantitative rather than qualitative.(Tomlinson et al., 1970; Arriagada et al., 1992)”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Introduction
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Alternatively, the presence of SPs and NFTs in nondemented older adults may represent AD at a stage prior to its clinical expression,(Morris et al., 1996; Price & Morris, 1999; Troncoso et al., 1998; Hulette et al., 1998; Schmitt et al., 2000) in which the neuropathological lesions of AD accumulate over many years before sufficient synaptic and neuronal damage occurs to produce the symptoms of AD.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Introduction
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Analysis was based on Bielschowsky-stained sections because they were more consistent, given the variable state of fixation of the material from different sources, although immunohistochemical sections (singly stained for Aβ or PHF, or double stained for both Aβ and PHF) were routinely examined and compared with the silver stained sections.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Material and Methods > Quantitative Assessment
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Both observers were “blind” to the clinical and CDR status of the cases and to the neuropathological findings determined by the ADCs contributing the cases.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Material and Methods > Neuropathological Procedures
plainn = 97- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The diagnoses were done by joint examination of each case by DWM and JLP, using a double-headed microscope to arrive at a consensus neuropathological diagnosis.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Material and Methods > Neuropathological Procedures
plainn = 97- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“Some studies have reported a negative effect for episodic memory only,(Hulette et al., 1998; Schmitt et al., 2000; Bennett et al., 2006) without effects in other cognitive domains, while other studies found no relationship between AD pathology and any cognitive measure.(Knopman et al., 2003; Driscoll et al., 2006)”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Introduction
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Although density measures may be affected by tissue shrinkage, the uniform treatment of the tissue (formalin fixation and paraffin embedding) and uniform staining in the central laboratory reduced variability.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Material and Methods > Quantitative Assessment
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Clinicians at each ADC verified the nondemented status for each case (the neuropathological diagnoses generated at the ADC performing the autopsy were not included in the eligibility criteria).”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Material and Methods > Participants
plainn = 97- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“all cases were coded so that the central laboratory was blind to the cognitive status of each case.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Material and Methods > Participants
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“The Neuropathology Core (JLP, DWM) of Washington University’s Alzheimer’s Disease Research Center served as the “central laboratory” to provide a standard and uniform neuropathological assessment of each case and avoid the variability introduced by different methods, criteria, and interpretations used at individual ADCs.(Mirra et al., 1994; Alafuzoff et al., 2006)”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Material and Methods > Neuropathological Procedures
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“while other studies found no relationship between AD pathology and any cognitive measure.(Knopman et al., 2003; Driscoll et al., 2006)”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Introduction
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“Previous studies of neuropathological AD in nondemented aging have been based on cases collected at a single site(Price & Morris, 1999; Galvin et al., 2005; Bennett et al., 2006), and comparison of results has been difficult because neuropathological methods and criteria differed in these studies.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Introduction
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Plaque burden was defined as the percent area occupied by plaques in relation to the total area sampled and is unaffected by tissue shrinkage.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Material and Methods > Quantitative Assessment
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“Earlier neuropathological studies also reported similar frequency of npAD in nondemented cases, including one reporting that 37.3% of 134 cognitively normal older adults, autopsied at a mean age between 82–85 years, met “Intermediate/High” NIA-Reagan criteria for npAD.(Bennett et al., 2006)”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
What the sources say
- Not checked yetcites Bennett et al., 2006 source
plainn = 134- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The NIA-Reagan criteria were not intended to characterize nondemented individuals or those with incipient dementia.(National Institute on Aging & Reagan Institute Working Group on Diagnostic Criteria for the Neuropathological Assessment of Alzheimer’s Disease, 1997)”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Material and Methods > Neuropathological Procedures
What the sources say
- Not checked yetcites National Institute on Aging & Reagan Institute Working Group on Diagnostic Criteria for the Neuropathological Assessment of Alzheimer’s Disease, 1997
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Neuropathological processes related to AD in persons without dementia appear to be associated with subtle cognitive dysfunction and may represent a preclinical stage of the illness.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Abstract > Conclusions
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In practice and research, however, the CERAD and NIA-Reagan criteria are much more commonly used.(Schmitt et al., 2000; Knopman et al., 2003; Bennett et al., 2006)”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Material and Methods > Neuropathological Procedures
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“However, SPs and NFTs characterize the neuropathological substrate of AD and synaptic and neuronal loss developing from these or other lesions appear to be critical for the expression of cognitive symptoms.(Masliah et al., 2001; Price et al., 2001)”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Another limitation was missing data in some cases, although there were almost no statistical differences for age at death, years of education, and gender between participants missing data for the last psychometric tests before death and those completing the tests. The only exception was Trailmaking A, where the mean years of education was 16.0 for participants with data vs. 14.4 for participants”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Results > Quantitative Neuropathological Assessment
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In this report, the Washington University criteria were considered “primary” because they were based on discriminative analyses of neuropathological data.(McKeel et al., 2004)”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Material and Methods > Neuropathological Procedures
What the sources say
- Not checked yetcites McKeel et al., 2004 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“Mismatches between NFT and SP densities are well-recognized(Dickson, 1995) and can present difficulties in categorization with NIA-Reagan criteria, which assume a strong correlation between NP density (reflected in the CERAD score) and NFT distribution (reflected in the Braak stage).(Geddes et al., 1997)”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
What the sources say
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Age-related neurofibrillary change may accelerate in the presence of Aβ lesions.(Price & Morris, 1999)”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
What the sources say
- Not checked yetcites Price & Morris, 1999
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Neuronal loss in the entorhinal cortex or hippocampal field CA1 has been shown to be absent in preclinical npAD compared with substantial cell loss in cases with equivalent neuropathological lesion burden but with symptomatic very mild DAT (CDR = 0.5).(Gomez-Isla et al., 1996; Price et al., 2001; West et al., 2004)”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
What the sources say
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The working group that formulated the NIA-Reagan criteria stated that the appearance of even one SP or NFT in the brain represents a pathological event, (National Institute on Aging & Reagan Institute Working Group on Diagnostic Criteria for the Neuropathological Assessment of Alzheimer’s Disease, 1997)”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
What the sources say
- Not checked yetcites National Institute on Aging & Reagan Institute Working Group on Diagnostic Criteria for the Neuropathological Assessment of Alzheimer’s Disease, 1997
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Limitations of the study include the use of a convenience sample, inability to assess a genotype effect, small sample sizes for some of the cognitive associations, and variability in initial fixation and tissue processing at individual ADCs that may have influenced immunohistochemical staining and quantitative measurement of neuritic SPs.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Subtle cognitive deficits can be detected many years before AD diagnosis(Elias et al., 2000; Kawas et al., 2003; Saxton et al., 2004; Tierney et al., 2005) but have not previously been correlated with AD lesions in nondemented individuals.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although not detectable in individual subjects, and insufficient to produce dementia, these deficits nonetheless suggest that the neurofibrillary and Aβ lesions, including diffuse SPs, exert deleterious effects.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The cognitive deficits associated with AD lesions in nondemented individuals are attributable to those lesions rather than to other pathologies or measurement error.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Finally, the sample of 97 individuals was sufficiently large to permit preliminary analyses of the cognitive correlates of AD lesions in the absence of dementia.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
plainn = 97- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“Another limitation is that SPs and NFTs may be downstream consequences of the pathophysiological processes responsible for the synaptic and neuronal degeneration that produces cognitive deficits in AD.(Shankar et al., 2008)”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
What the sources say
- Not checked yetcites Shankar et al., 2008 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Limitations of the study include the use of a convenience sample, inability to assess a genotype effect, small sample sizes for some of the cognitive associations, and variability in initial fixation and tissue processing at individual ADCs that may have influenced immunohistochemical staining and quantitative measurement of neuritic SPs.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Third, because there remains inter-laboratory variation in assessing AD lesions and consequently in neuropathological diagnosis,(Alafuzoff et al., 2006) the contributed sections were processed uniformly and interpreted at one center.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
What the sources say
- Not checked yetcites Alafuzoff et al., 2006 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Limitations of the study include the use of a convenience sample, inability to assess a genotype effect, small sample sizes for some of the cognitive associations, and variability in initial fixation and tissue processing at individual ADCs that may have influenced immunohistochemical staining and quantitative measurement of neuritic SPs.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The findings of this study are consistent with (but do not prove) the concept of preclinical AD.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The autopsy sample of nondemented older adults is representative enough that the estimated frequency of npAD applies to nondemented older adults generally.
- Rests on an assumption: The cognitive deficits associated with AD lesions in nondemented individuals are attributable to those lesions rather than to other pathologies or measurement error.
None of the sources cited for this claim have been checked yet.
In the paper
“The pathobiological relevance of even diffuse SPs for AD is consistent with evidence that soluble Aβ dimers and oligomers, prior to the stage of SPs, have neurotoxic effects(Hung et al., 2008) and are associated with decreases in long term potentiation, dendritic spine density, and memory performance in experimental models.(Shankar et al., 2008)”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Limitations of the study include the use of a convenience sample, inability to assess a genotype effect, small sample sizes for some of the cognitive associations, and variability in initial fixation and tissue processing at individual ADCs that may have influenced immunohistochemical staining and quantitative measurement of neuritic SPs.”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“For example, neurofibrillary lesions may have greater relevance for cognitive impairment once the clinical symptoms of AD are expressed.(Bennett et al., 2004)”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
What the sources say
- Not checked yetcites Bennett et al., 2004 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“for example, SPs and NFTs may elicit a host response that contributes to the neurotoxicity of AD.(Castellani et al., 2008)”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
What the sources say
- Not checked yetcites Castellani et al., 2008 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“This study did not address the early protein changes that lead to SPs and NFTs or the later synaptic or neuronal loss and other potential factors (e.g., vascular lesions; synucleinopathy) that could contribute to cognitive dysfunction; for example, SPs and NFTs may elicit a host response that contributes to the neurotoxicity of AD.(Castellani et al., 2008)”
§ Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper relies on this without support.
The autopsied sample from seven Alzheimer Disease Centers is representative of nondemented older adults in the general population.
“By age 80–85 years, many nondemented older adults have substantial AD pathology.”
The paper relies on this without support.
The observed associations between Alzheimer disease lesions and cognitive test scores are not due to other brain pathologies or unmeasured confounders.
“In all cases, greater pathology was associated with poorer cognitive performance at last assessment on measures of episodic memory (Logical Memory Delayed), semantic knowledge (Category Fluency), visuospatial ability (Trailmaking A), and executive function (Trailmaking B) as well as on a general measure, the MMSE.”
The paper relies on this without support.
The four published neuropathological criteria validly classify neuropathological Alzheimer disease in nondemented older adults even though they were developed for dementia.
“Each case was assessed in accordance with 4 published criteria for the neuropathological diagnosis of AD.”
The paper relies on this without support.
The autopsy sample of nondemented older adults is representative enough that the estimated frequency of npAD applies to nondemented older adults generally.
“The finding that up to 40% of nondemented individuals with a mean age of death of 84 years have npAD corresponds with some estimates of the prevalence of clinically apparent DAT in this age group.(Hebert et al., 2003)”
The paper relies on this without support.
The cognitive deficits associated with AD lesions in nondemented individuals are attributable to those lesions rather than to other pathologies or measurement error.
“This study did not address the early protein changes that lead to SPs and NFTs or the later synaptic or neuronal loss and other potential factors (e.g., vascular lesions; synucleinopathy) that could contribute to cognitive dysfunction; for example, SPs and NFTs may elicit a host response that contributes to the neurotoxicity of AD.(Castellani et al., 2008)”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“However, there is only a weak correlation between the degree of cognitive impairment and the presence of plaques or neurofibrillary tangles (Price et al., 2009)”
From The influence of phospho-tau on dendritic spines of cortical pyramidal neurons in patients with Alzheimer’s disease (2013) · cites this paper as Price et al., 2009
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Among individuals who showed no overt evidence of cognitive impairment in the final assessment prior to death, post-mortem studies showed a significant proportion of subjects with neuropathological diagnoses of AD”
From Repair of Oxidative DNA Damage, Cell-Cycle Regulation and Neuronal Death May Influence the Clinical Manifestation of Alzheimer’s Disease (2014) · cites this paper as [10]
The cited source says what the claim attributes to it.
In the citing paper
“It is important to note that Aβ deposition is not exclusive to individuals with AD as it can be found also in nondemented elderly individuals (64).”
From Modeling late-onset Alzheimer’s disease neuropathology via direct neuronal reprogramming (2024) · cites this paper as [64]
The cited source says what the claim attributes to it.
In the citing paper
“several studies have revealed the existence of aged individuals harboring a high burden of brain lesions at autopsy while remaining cognitively intact, indicating resilience to AD pathology [3, 7, 21, 22, 56, 57, 68, 76, 78, 96].”
From Enhanced microglial dynamics and a paucity of tau seeding in the amyloid plaque microenvironment contribute to cognitive resilience in Alzheimer’s disease (2024) · cites this paper as [76]
In the citing paper
“Supporting this notion, Price et al. reported no measureable cognitive impairment per se in such preclinical AD cases, but degraded cognitive function in the presence of plaques and tangles (Price, et al., 2009).”
From Cellular, synaptic, and biochemical features of resilient cognition in Alzheimer’s disease (2013) · cites this paper as Price, et al., 2009
In the citing paper
“Neuropathological studies in humanshave demonstrated that tau pathology generally does not progress from the entorhinal cortex into the neocortex in the absence of co-occurring amyloid pathology”
From Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019) · cites this paper as Price et al., 2009
In the citing paper
“Cognitive impairment in AD is only noted when tau spreads from the entorhinal cortex into the neocortex in neuropathological studies”
From Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019) · cites this paper as Price et al., 2009
In the citing paper
“Some of the variability may be due to the evolution of the NP as part of the disease process (52-54).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [54]
In the citing paper
“Subtle cognitive impairment may be associated with diffuse AβPs, indicating that these lesions may play a direct role in incipient AD (54), although a direct role of diffuse Aβ plaques without tau pathology has not been proven.”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [54]
In the citing paper
“We are aware of no reported case of truly intact cognition despite extremely severe AD pathologic changes (i.e. widespread neocortical NFTs) measured with quantitative pathologic analysis, although many persons with intact cognition have been assessed in autopsy series (33, 42, 54, 133, 142, 148, 151-166).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [54]
Citations
Cites
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Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123
The Clinical Dementia Rating (CDR): Current version and scoring rules
Morris, J. C. (1993) · Neurology · doi:10.1212/wnl.43.11.2412-a · Cited by 9,882
Self-citationMirra, S. S., Heyman, A., McKeel, D., Sumi, S. M., Crain, B. J., Brownlee, L. M., Vogel, F. S., Hughes, J. P., Belle, G. V., Berg, L., et al. (1991) · Neurology · doi:10.1212/wnl.41.4.479 · Cited by 4,961
Self-citationImaging brain amyloid in Alzheimer's disease with Pittsburgh Compound‐B
Klunk, W. E., Engler, H., Nordberg, A., Wang, Y., Blomqvist, G., Holt, D. P., Bergström, M., Savitcheva, I., Huang, G., Estrada, S., et al. (2004) · Annals of Neurology · doi:10.1002/ana.20009 · Cited by 4,496
Self-citationShankar, G. M., Li, S., Mehta, T. H., Garcia-Munoz, A., Shepardson, N. E., Smith, I., Brett, F. M., Farrell, M. A., Rowan, M. J., Lemere, C. A., et al. (2008) · Nature Medicine · doi:10.1038/nm1782 · Cited by 3,685
The assessment of aphasia and related disorders
Goodglass, H., & Kaplan, E. (1972) · Medical Entomology and Zoology · Cited by 3,258
Diagnosis of Alzheimer's Disease
Khachaturian, Z. S. (1985) · Archives of Neurology · doi:10.1001/archneur.1985.04060100083029 · Cited by 2,499 · cited 1×
“Consenus criteria reported by Khachaturian (1985) are based on he highest density of total SPs (diffuse and neuritic) in any ortical field, adjusted for age (the greater the age of the indiidual, the greater the density required for diagnosis).”
BackgroundAssessment of Aphasia and Related Disorders
Sarno, M. T. (1973) · Physical Therapy · doi:10.1093/ptj/53.2.225b · Cited by 2,256
Alzheimer Disease in the US Population: Prevalence Estimates Using the 2000 Census
Hebert, L. E., Scherr, P. A., Bienias, J. L., Bennett, D. A., & Evans, D. A. (2003) · Archives of Neurology · doi:10.1001/archneur.60.8.1119 · Cited by 2,168
Cited by
Sorted by citations
Neuropathological alterations in Alzheimer disease
Serrano-Pozo, A., Frosch, M. P., Masliah, E., & Hyman, B. T. (2011) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006189 · Cited by 3,345
Alzheimer Disease: An Update on Pathobiology and Treatment Strategies
Long, J. M., & Holtzman, D. M. (2019) · Cell · doi:10.1016/j.cell.2019.09.001 · Cited by 3,204
Hyman, B. T., Phelps, C. H., Beach, T. G., Bigio, E. H., Cairns, N. J., Carrillo, M. C., Dickson, D. W., Duyckaerts, C., Frosch, M. P., Masliah, E., et al. (2012) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.10.007 · Cited by 3,092
Self-citationVillemagne, V. L., Burnham, S., Bourgeat, P., Brown, B., Ellis, K. A., Salvado, O., Szoeke, C., Macaulay, S. L., Martins, R., Maruff, P., et al. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70044-9 · Cited by 2,279
Karran, E., Mercken, M., & Strooper, B. D. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3505 · Cited by 2,188
Metadata
- Authors
- Price, J. L., McKeel, D. W., Buckles, V. D., Roe, C. M., Xiong, C., Grundman, M., Hansen, L. A., Petersen, R. C., Parisi, J. E., Dickson, D. W., Smith, C. D., Davis, D. G., Schmitt, F. A., Markesbery, W. R., Kaye, J., Kurlan, R., Hulette, C., Kurland, B. F., Higdon, R., Kukull, W., & Morris, J. C.
- Affiliations
- Washington University in St. Louis (US)
- Elan Pharmaceuticals, Inc. (Ireland) (IE)
- University of California San Diego (US)
- Mayo Clinic (US)
- University of Kentucky (US)
- Central Baptist Hospital (US)
- Oregon Health & Science University (US)
- University of Rochester Medicine (US)
- Duke University (US)
- Fred Hutch Cancer Center (US)
- University of Washington (US)
- Corresponding author
- Morris, John C.
- ORCID
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2009-07
- Volume
- 30
- Issue
- 7
- Pages
- 1026-1036
- ISSN
- 0197-4580 (ISSN-L)
- PMC
- PMC2737680
- OpenAlex
- W2114222094
- Semantic Scholar
- 56b77cd6ec3334e93ca55ab8412c4c9a608abbd6
- Cited by
- 661
- References
- 65
- Citations by year
- 2026: 17 · 2025: 17 · 2024: 21 · 2023: 29 · 2022: 31 · 2021: 38 · 2020: 30 · 2019: 37 · 2018: 48 · 2017: 34 · 2016: 54 · 2015: 49 · 2014: 47 · 2013: 38 · 2012: 60
- FWCI
- 34.43
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR000448)
- National Institute on Aging (P30AG028383, P30AG028377, U01AG016976, P50AG005131, P30AG008017, U01-AG 16976, P 50 AG05681, P50AG005681, P01 AG0 3991, P01AG003991, P30AG008665, P01AG026276, P50AG016574)
- National Center for Research Resources (UL1RR024992)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- preclinical Alzheimer's disease, Alzheimer's disease pathology, amyloid plaques, neurofibrillary tangles, cognitive impairment, older adults
- MeSH terms
- Aged, Aged, 80 and over, Aging, Alzheimer Disease, Brain, Cognition Disorders, Female, Humans, Male, Middle Aged, Neuropsychological Tests, Psychometrics, Severity of Illness Index, Statistics as Topic, Linear Models, Neurofibrillary Tangles, Age Distribution, Disease Progression, Early Diagnosis, Plaque, Amyloid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-05, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-05 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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